Risk Factors for Development of Hypocalcemia in Patients With Cancer Treated With Bone-Modifying Agents.

BACKGROUND: This retrospective analysis describes the prevalence of and risk factors associated with the development of hypocalcemia in patients with cancer receiving bone-modifying agents (BMAs) as supportive care. PATIENTS AND METHODS: Patients with cancer treated with an intravenous or subcutaneous BMA, including pamidronate, zoledronic acid, or denosumab, at a tertiary care/safety net hospital in 2005 through 2015 were included in this retrospective review. We reviewed the medical records for predictive clinical and laboratory parameters and for patient outcomes. RESULTS: A total of 835 patients with cancer received at least one dose of a BMA during the specified time frame; 205 patients (25%) developed hypocalcemia of CTCAE grade ≥1 within 8 weeks of BMA initiation, 18 of whom (8.8%) had grade ≥3, and 3 patients died as a result. Multivariate analysis showed that patients with hematologic malignancy (odds ratio [OR], 1.956; P=.025), bone metastases (OR, 2.443; P=.017), inpatient status (OR, 2.592; P<.001), and deficient baseline vitamin D levels (OR, 2.546; P<.023) were more likely to develop hypocalcemia. Hypercalcemia before BMA administration (OR, 0.474; P=.032) was protective. CONCLUSIONS: Certain patient populations, including those with hematologic malignancies and/or bone metastases, warrant closer monitoring of calcium levels while receiving BMAs because of the high rate of hypocalcemia. Low pretreatment vitamin D levels are associated with the development of hypocalcemia. These data support close monitoring of calcium levels in patients with cancer receiving BMAs, in addition to adequate repletion of vitamin D before initiation of BMAs when possible.

Management of Fibromyalgia: An Update.

Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function. Hallmark symptoms include widespread persistent pain, sleep disturbances, fatigue, cognitive dysfunction, and mood changes. Through this updated review, we aim to contribute to the evolving understanding and management of fibromyalgia, offering insights into the diverse tools available to improve the lives of those affected by this challenging condition. Management begins with educating patients to ultimately relieve them of unnecessary testing and provide reassurance. Treatment emphasizes a comprehensive approach, combining nonpharmacological interventions such as aforementioned education, exercise, and psychotherapy, alongside pharmacologic management-namely duloxetine, milnacipran, pregabalin, and amitriptyline-which have consistent benefits for a range of symptoms across the spectrum of fibromyalgia. Notably, drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are generally not recommended due to limited efficacy and associated risks. Lastly, a variety of other medications have shown promise, including NMDA-receptor antagonists, naltrexone, and cannabinoids; however, they should be used with caution due to a small amount of evidence and potential for adverse effects.

Confirmation and inheritance of glufosinate resistance in an Amaranthus palmeri population from North Carolina.

A putative glufosinate-resistant Amaranthus palmeri population was reported in 2015 in Anson County, North Carolina. The results from dose-response assays conducted in the field suggested plants were surviving lethal rates of glufosinate. Dose-response assays conducted in the glasshouse determined the Anson County accession exhibited reduced susceptibility to glufosinate compared to three glufosinate-susceptible populations. The LD50 values (210-316 g ai ha-1) for the Anson County population were always higher than the LD50 values (118-158 g ai ha-1) for the tested susceptible populations from the dose-response assays. Anson County plants that survived lethal glufosinate rates were reciprocally crossed with susceptible plants to create F1 genotypes and treated with a lethal rate of glufosinate (267 g ai ha-1; ascertained from glasshouse dose-response assay) to determine the distribution of injury and survival for each cross compared to a cross of susceptible parents. The distribution of injury was non-normal for the crosses containing an Anson County plant compared to the cross with a susceptible parent. Survival was 68%-84% for crosses containing an Anson County plant, whereas the survival was significantly reduced to 35% for the susceptible plant cross. Chi-square goodness of fit tests were used to test inheritance models to describe the responses of the genotypes. The resistant × susceptible crosses were best described with a heterozygous two loci with incomplete dominance model compared to the resistant × resistant cross that was best described with a heterozygous single locus with incomplete dominance model. The Anson County population has evolved resistance to glufosinate that is heritable and likely conferred by an oligogenic mechanism with incomplete dominance.

Durability of Near-Complete Skin Clearance in Patients with Psoriasis Using Systemic Biologic Therapies: Real-World Evidence from the CorEvitas Psoriasis Registry.

INTRODUCTION: Near-complete skin clearance has become a rapidly achievable treatment goal for patients with psoriasis receiving systemic biologic therapies. However, real-world evidence for durability of near-complete skin clearance and risk factors associated with loss of near-complete skin clearance is limited. METHODS: This study described durability of near-complete skin clearance (≥ 90% improvement in Psoriasis Area and Severity Index from initiation; PASI90) and identified clinical factors or patient characteristics associated with loss of PASI90 among patients with psoriasis from the CorEvitas Psoriasis Registry (April 2015-August 2021). Included patients had PASI > 5 at biologic initiation and achieved PASI90 at approximately 6 months from initiation (index). A Kaplan-Meier estimate described time to loss of treatment response over 24 months follow-up from index. Proportional hazards regression was used to identify independent predictors of loss of treatment response. RESULTS: This study included 687 patient initiations (instances of patients initiating a biologic). Following achievement of PASI90, treatment response was maintained in more than half of patient initiations (54%). Treatment response was maintained at 6, 12, and 18 months from index in an estimated 73% (95% [confidence interval] CI 70-77%), 60% (95% CI 56-63%), and 50% (95% CI 47-54%) of patient initiations, respectively. Adjusted hazards regression suggested non-White race, full-time employment, greater body weight, concomitant psoriatic arthritis, prior use of biologics, and clinically meaningful skin symptoms were associated with loss of treatment response. CONCLUSIONS: Among real-world patients with psoriasis who achieved PASI90 with biologic therapy, about one-quarter lost response at 6 months, and half lost response at 18 months. Prior use of a biologic therapy and clinically meaningful skin symptoms at index, including itch and skin pain, were associated with loss of treatment response. Therefore, dermatologists may consider focusing on patient-reported symptoms as part of any intervention designed to reduce the likelihood of loss of response to biologic therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02707341.

Many people with psoriasis are treated with biologic medications that work to improve symptoms associated with psoriasis, including inflammation. These medications can lead to almost clear skin for many people. However, there is limited information available about how long almost clear skin can be maintained with biologic medications, and what predicts who is likely to lose it. To explore these questions, we examined a database of patients with psoriasis (the CorEvitas Psoriasis Registry) that records how clear patients' skin is and the medications they take. Out of every 100 patients, 54 maintained almost clear skin and stayed on their original medication for 2 years after first having almost clear skin. Out of every 100 patients, 73, 60, and 50 maintained almost clear skin and remained on their original medication at 6, 12, and 18 months after they had achieved this response. The results indicated that patients who were not White, worked full time, previously used a biologic medication, or had itchy and/or painful skin after they had achieved almost-clear skin were more likely to change their medication and/or no longer have almost-clear skin. These results suggest that dermatologists may consider focusing on patient-reported characteristics when deciding how to treat their patients, to reduce the likelihood that they lose their response to the medication they are prescribed.

Disease burden among patients with atopic dermatitis treated with systemic therapy for 4-12 months: results from the CorEvitas Atopic Dermatitis Registry.

BACKGROUND: Real-world data on the effectiveness of systemic therapy in atopic dermatitis (AD) are limited. METHODS: Adult patients with AD in the CorEvitas AD registry (2020-2021) who received systemic therapies for 4-12 months prior to enrollment were included based on disease severity: body surface area (BSA) 0%-9% and BSA ≥10%. Demographics, clinical characteristics, and outcomes were assessed using descriptive statistics. Pairwise effect sizes (ES) were used to compare BSA groups. RESULTS: The study included 308 patients (BSA 0%-9%: 246 [80%]; BSA ≥10%: 62 [20%]). Despite systemic therapy, both BSA groups reported the use of additional topical therapy and the presence of lesions at difficult locations. Moderate-to-severe AD (vIGA-AD®) was reported by 11% (BSA 0%-9%) and 66% (BSA ≥10%; ES = 0.56) of patients. Mean disease severity scores: total BSA (2% and 22%; ES = 3.59), EASI (1.1 and 11.1; ES = 2.60), and SCORAD (12.1 and 38.0; ES = 1.99). Mean scores for PROs: DLQI (3.7 and 7.5; ES = 0.75), and peak pruritus (2.2 and 4.5; ES = 0.81). Inadequate control of AD was seen in 27% and 53% of patients (ES = 0.23). CONCLUSIONS: Patients with AD experience a high disease burden despite systemic treatment for 4-12 months. This study provides potential evidence of suboptimal treatment and the need for additional effective treatment options for AD.

This real-world study assessed clinical characteristics and overall disease burden in adult patients with atopic dermatitis (AD) who were receiving systemic therapy for 4­12 months.Patients reported greater involvement of back and anterior trunk, and lesions at difficult locations. Irrespective of body surface area involvement, patients continued to experience inadequate control of AD, varied disease severity, and impact on quality of life.The study provides potential evidence of suboptimal treatment and the need for effective treatment options for the management of AD. Besides clinical outcomes, treating dermatologists and dermatology practitioners should include patient-reported outcomes in routine clinical care to determine the best treatment options for their patients.

Trends from 2005 to 2018 in child maltreatment outcomes with caregivers' substance use.

BACKGROUND: Caregivers' substance use is associated with child maltreatment. OBJECTIVE: Examine trends from 2005 to 2018 in percentages of three outcomes with caregivers' drug or alcohol use: child protective services (CPS) referrals, substantiated maltreatment reports, and foster care placements. PARTICIPANTS AND SETTING: 22 U.S. states that contributed child-level maltreatment outcomes and caregivers' substance use data to the National Child Abuse and Neglect Data System from 2005 to 2018. METHODS: Joinpoint regression was used to examine the average annual percent change (AAPC) in outcomes with caregivers' drug or alcohol use and to identify temporal changes. RESULTS: From 2005 to 2018, CPS referrals with caregivers' drug use increased (AAPC 2.33, p < .001), while referrals with alcohol use remained unchanged (AAPC -0.11, p = .92) (trend difference p = .04). Substantiated reports with caregivers' drug and alcohol use increased (AAPC drug use 3.63, p < .001, AAPC alcohol use 1.28, p = .03), with a greater increase observed with drug use (difference p = .03). Foster care placements with caregivers' drug use increased (AAPC 2.54, p < .001), while placements with alcohol use did not change (AAPC -1.22, p = .29), (difference p = .005). Within the study period, changes in trends with caregivers' drug use included increased substantiated reports from 2010 to 2018 (p < .001) and increased foster care placements from 2009 to 2018 (p < .001). With caregivers' alcohol use, CPS referrals and foster care placements decreased from 2007 to 2018 (all p < .001). CONCLUSIONS: Trends differed for outcomes with caregivers' drug versus alcohol use. Findings can inform policies to improve care for families affected by substance use.

Cross-sectional evaluation of parental decision making factors for vesicoureteral reflux management in children.

PURPOSE: Parental decision making in children with vesicoureteral reflux has potentially become more complex with the evolution of ethnic diversity in the United States, the Internet, the publication of contradictory clinical data and the emergence of minimally invasive surgery. We performed a cross-sectional study of parental management for pediatric vesicoureteral reflux. MATERIALS AND METHODS: We administered a 26-item questionnaire to parents of children with vesicoureteral reflux seen at Texas Children's Hospital urology offices or undergoing antireflux surgery at that institution. Univariate and multivariate analysis was done on patient disease characteristics, demographics, predicted reflux duration, surgery success rate, antibiotic cessation, complication risk, financial considerations, urologist recommendations, Internet information, friend recommendations, and postoperative voiding cystourethrography, renal ultrasound and recovery. RESULTS: Enrolled in the study were 15 boys and 49 girls with a mean age of 3.5 years and a mean reflux grade of 2.8. Of the cases 37 were bilateral. Parents chose endoscopic treatment in 38 children, open ureteroneocystostomy in 9, antibiotic prophylaxis in 14 and observation without antibiotics in 3. Univariate analysis suggested that Hispanic parents rated ultrasound and financial considerations as more important than white parents (p <0.05). Multivariate analysis revealed that differences seen on univariate analysis may have been due to an association between race and income. Finally, 93.6% of parents rated urologist opinion as very or extremely important. CONCLUSIONS: Data indicate that the parents of our patients highly value the opinion of the pediatric urologist when choosing treatment for their children with vesicoureteral reflux. Despite social changes the physician-parental relationship remains critical. Differences in parental decision making may be linked to associations between race and income.

Factors associated with delayed treatment of acute testicular torsion-do demographics or interhospital transfer matter?

PURPOSE: Testicular torsion is a true urological emergency. We determined whether a delay in treatment due to hospital transfer or socioeconomic factors would impact the orchiectomy rate in children with this condition. MATERIALS AND METHODS: We retrospectively evaluated the records of boys seen at a single institution emergency department who proceeded to surgery for a diagnosis of acute testicular torsion from 2003 to 2008. Charts were reviewed for transfer status, symptom duration, race, insurance presence or absence and distance from the hospital. Orchiectomy specimens were evaluated for histological confirmation of nonviability. RESULTS: We reviewed 97 records. The orchiectomy rate in patients who were vs were not transferred to the emergency department was 47.8% vs 68.9%, respectively (p = 0.07). Symptom duration was greater in the orchiectomy group with a mean difference of 47.9 hours (p <0.01). The mean transfer delay was 1 hour 15 minutes longer in the orchiectomy group (p = 0.01). Boys who underwent orchiectomy were 2.2 years younger than those who avoided orchiectomy (p = 0.01). Multivariate analysis showed that symptom duration and distance from the hospital were the strongest predictors of orchiectomy. CONCLUSIONS: Data suggest that torsion is a time dependent event and factors that delay time to treatment lead to poorer outcomes. These factors include distance from the hospital and the time delay associated with hospital transfer.

Education and insurance status: Impact on treatment and survival of sinonasal cancer patients.

OBJECTIVES/HYPOTHESIS: To understand the impact of education and insurance as social determinants of health on sinonasal cancer treatment and outcomes. STUDY DESIGN: Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Demographics, tumor characteristics, location, stage at diagnosis, treatment, and survival data for 1,365 patients diagnosed with sinonasal cancers were extracted from the SEER database. All statistical analyses were performed using SAS 9.5. The Fine and Grey method was used to assess covariate impacts. RESULTS: Medicaid patients were more likely to live in counties with lower educational levels (8.32% vs. 6.46% below ninth grade education, P < .0001) and lower median household incomes ($56,316 vs. $60,284, P = .0004). Medicaid patients presented with later (T3-T4) stage disease compared to other insurances (P = .0007) and larger tumor size (P = .011). Medicaid patients were less likely to have surgery recommended (P = .0017) or receive surgery as part of their treatment (P = .0033). Analysis of histology-specific 5-year survival rates were lower for Medicaid patients with squamous cell carcinoma (SCCA) (P = .016). CONCLUSIONS: This is the first and largest study to examine how education and insurance status may impact treatment and outcomes in sinonasal cancers. It is the first using this method of examining other covariates and informing associated risk. Patients with Medicaid and less education present with larger sinonasal cancers. They are less likely to have surgery recommended or receive surgery. For SCCA, the most common histology, Medicaid patients have significantly worse survival. Further emphasis on education and improving health literacy is needed in the at-risk Medicaid populations. LEVEL OF EVIDENCE: NA Laryngoscope, 130:649-658, 2020.

Social Determinants of Health and Oral Cavity Cancer Treatment and Survival: A Competing Risk Analysis.

OBJECTIVE: Competing risk analysis is a powerful assessment for cancer risk factors and covariates. This method can better elucidate insurance status and other social determinants of health covariates in oral cavity cancer treatment, survival, and disparities. STUDY DESIGN: Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Data regarding patient characteristics, clinical stage at diagnosis, treatment, and survival data for 20,271 patients diagnosed with oral cavity cancer was extracted from the SEER 18 Regs Research Data including Hurricane Katrina Impacted Louisiana Cases from 1973 to 2014. All statistical analyses were performed using SAS 9.5 (SAS Institute Inc., Cary, NC). The Fine-Gray method for assessing impact, risk, and covariates was employed. RESULTS: Medicaid patients presented with later stage disease, larger tumor size, more distant metastases, and more lymph node involvement at diagnosis compared to insured patients. Medicaid patients were less likely to receive cancer-directed surgery. Medicaid status was also associated with worse cancer-specific survival (subhazard ratios 1.87, 95% confidence interval 1.72-2.04, P < .0001) after adjustment for all covariates. CONCLUSION: This is the first study examining specifically how Medicaid status and social determinants of health covariates impact oral cavity cancer treatment and outcomes and is the first using methods validated for complex covariates. Patients with Medicaid present with more extensive oral cavity disease burden are less likely to receive definitive therapy and have significantly worse overall survival than those with other forms of insurance. This better identifies disparities and the need for improving health literacy, specifically for the at-risk Medicaid population, and can guide clinicians. LEVEL OF EVIDENCE: NA Laryngoscope, 130:2160-2165, 2020.

Bladder injuries during laparoscopic orchiopexy: incidence and lessons learned.

PURPOSE: Laparoscopic orchiopexy is a safe operation. However, the bladder can be injured during creation of the transperitoneal tunnel for the cryptorchid testis. We reviewed our experience with this complication. MATERIALS AND METHODS: We searched the operative notes of patients who had undergone laparoscopic orchiopexy between August 15, 2002 and October 1, 2008, and identified bladder injuries and their treatment. RESULTS: A total of 93 patients underwent laparoscopic orchiopexies for 101 undescended testes during the study interval, with 3 procedures resulting in bladder injuries. The 3 operations varied with regard to whether the injury was recognized intraoperatively or postoperatively, and repaired in an open or laparoscopic fashion. CONCLUSIONS: Bladder injury during laparoscopic orchiopexy is a rare but serious complication that can be managed by an open or laparoscopic approach. We recommend placement of a urethral catheter and syringe assisted drainage of all urine from the bladder at the beginning of the operation, careful perivesical dissection particularly in children with prior inguinal surgery, filling and emptying of the bladder during the procedure, and maintaining a high index of suspicion especially when hematuria is observed.

Budgetary impact analysis of a primary care-based hepatitis C treatment program: Effects of 340B Drug Pricing Program.

PURPOSE: Safety-net health systems, which serve a disproportionate share of patients at high risk for hepatitis C virus (HCV) infection, may use revenue generated by the federal drug discount pricing program, known as 340B, to support multidisciplinary care. Budgetary impacts of repealing the drug-pricing program are unknown. Our objective was to conduct a budgetary impact analysis of a multidisciplinary primary care-based HCV treatment program, with and without 340B support. METHODS: We conducted a budgetary impact analysis from the perspective of a large safety-net medical center in Boston, Massachusetts. Participants included 302 HCV-infected patients (mean age 45, 75% male, 53% white, 77% Medicaid) referred to the primary care-based HCV treatment program from 2015-2016. Main measures included costs and revenues associated with the treatment program. Our main outcomes were net cost with and without 340B Drug Pricing support. RESULTS: Total program costs were $942,770, while revenues totaled $1.2 million. With the 340B Drug Pricing Program the hospital received a net revenue of $930 per patient referred to the HCV treatment program. In the absence of the 340B program, the hospital would lose $370 per patient referred. Ninety-seven percent (68/70) of patients who initiated treatment in the program achieved a sustained virologic response (SVR) at a net cost of $4,150 each, among this patient subset. CONCLUSIONS: The 340B Drug Pricing Program enabled a safety-net hospital to deliver effective primary care-based HCV treatment using a multidisciplinary care team. Efforts to sustain the 340B program could enable dissemination of similar HCV treatment models elsewhere.

Fibronectin binding and proteolytic degradation by Leishmania and effects on macrophage activation.

Infection by vector-borne protozoa of the genus Leishmania occurs by the deposition of parasites within the skin of the mammalian host, where they eventually bind to and are phagocytized by Mphis. Our previous work supported the idea that parasites can interact with extracellular matrix and basement membrane proteins, such as fibronectin (FN), within the skin, leading to enhanced invasion. In this report, we extend these findings and show that both promastigotes and amastigotes of Leishmania species can bind directly to soluble FN and laminin (LM) and that promastigotes express a distinct surface protein of approximately 60 kDa that binds both FN and LM. Promastigotes of multiple Leishmania species can rapidly degrade FN by using surface-localized and secreted metalloprotease (leishmanolysin). FN degradation at the surfaces of amastigotes is leishmanolysin dependent, whereas both secreted leishmanolysin and cysteine protease B contribute to extracellular FN degradation. Leishmania-degraded FN decreased the production of reactive oxygen intermediates by parasite-infected macrophages and affected the accumulation of intracellular parasites. These findings show that both parasite stages of Leishmania species bind to and proteolytically degrade FN at the parasite surface and distantly through secreted proteases and that degraded forms of FN can influence the activation state of parasite-infected macrophages.

Primer: diagnosis and management of uncomplicated daytime wetting in children.

Functional daytime wetting is a common source of pediatric urologic complaints. Evaluation typically begins in the office setting. In contrast to the adult population, where an inability to maintain voiding control is virtually always considered pathologic, the evaluation of urinary incontinence in children must occur within the context of the child's developmental age. Functional incontinence refers to cases of urinary incontinence in which no structural or neurologic abnormality can be identified. The underlying etiologic mechanisms are heterogeneous, and include disorders of both the storage and voiding phases of the bladder cycle. Optimal treatment of functional daytime wetting depends on an accurate determination of the underlying etiology. Therapeutic options include behavior modification, medication, and aggressive treatment of comorbid conditions such as urinary infection and constipation.

Megalourethra and urethral diverticula.

Megalourethra and urethral diverticula encompass a diverse group of congenital and acquired urethral defects. The appropriate management of these anomalies relies on a keen appreciation of phallic anatomy and an understanding of urethral embryology. A thorough history and physical examination--including a careful evaluation of the urinary tract--is necessary to identify associated congenital anomalies. Finally, satisfactory surgical management demands meticulous attention to surgical technique.

Copy number variation of the beta defensin gene cluster on chromosome 8p influences the bacterial microbiota within the nasopharynx of otitis-prone children.

As there is increasing evidence that aberrant defensin expression is related to susceptibility for infectious disease and inflammatory disorders, we sought to determine if copy number of the beta-defensin gene cluster located on chromosome 8p23.1 (DEFB107, 106, 105, 104, 103, DEFB4 and SPAG11), that shows copy number variation as a block, was associated with susceptibility to otitis media (OM). The gene DEFB103 within this complex encodes human beta defensin-3 (hBD-3), an antimicrobial peptide (AP) expressed by epithelial cells that line the mammalian airway, important for defense of mucosal surfaces and previously shown to have bactericidal activity in vitro against multiple human pathogens, including the three that predominate in OM. To this end, we conducted a retrospective case-control study of 113 OM prone children and 267 controls aged five to sixty months. We identified the copy number of the above defined beta-defensin gene cluster (DEFB-CN) in each study subject by paralogue ratio assays. The mean DEFB-CN was indistinguishable between subjects classified as OM prone based on a recent history of multiple episodes of OM and control subjects who had no history of OM (4.4 ± 0.96 versus 4.4 ± 1.08, respectively: Odds Ratio [OR]: 1.16 (95% CI: 0.61, 2.20). Despite a lack of direct association, we observed a statistically significant correlation between DEFB-CN and nasopharyngeal bacterial colonization patterns. Collectively, our findings suggested that susceptibility to OM might be mediated by genetic variation among individuals, wherein a DEFB-CN less than 4 exerts a marked influence on the microbiota of the nasopharynx, specifically with regard to colonization by the three predominant bacterial pathogens of OM.

Extracellular DNA within a nontypeable Haemophilus influenzae-induced biofilm binds human beta defensin-3 and reduces its antimicrobial activity.

Biofilms formed by nontypeable Haemophilus influenzae (NTHI) are associated with multiple chronic infections of the airway, including otitis media. Extracellular DNA (eDNA) is part of the biofilm matrix and serves as a structural component. Human ß-defensin-3 (hBD-3) is a cationic antimicrobial host defense protein (AMP) critical to the protection of the middle ear. We hypothesized that anionic eDNA could interact with and bind hBD-3 and thus shield NTHI in biofilms from its antimicrobial activity. We demonstrated that recombinant hBD-3 [(r)hBD-3] bound eDNA in vitro and that eDNA in biofilms produced by NTHI in the chinchilla middle ear co-localized with the orthologue of this AMP. Incubation of physiological concentrations of (r)hBD-3 with NTHI genomic DNA abrogated the ability of this innate immune effector to prevent NTHI from forming robust biofilms in vitro. Establishment of NTHI biofilms in the presence of both DNase I and (r)hBD-3 resulted in a marked reduction in the overall height and thickness of the biofilms and rescued the antimicrobial activity of the AMP. Our results demonstrated that eDNA in NTHI biofilms sequestered hBD-3 and thus diminished the biological activity of an important effector of innate immunity. Our observations have important implications for chronicity of NTHI-induced diseases.